Background Gastroesophageal reflux disease (GERD), functional dyspepsia (FD), and irritable bowel syndrome (IBS) are common gastrointestinal diseases. Several studies have shown a significant occurrence of overlap among these 3 diseases. The purpose of this study was to examine the factors associated with such disease overlap in Japanese adults. Methods We performed a cross-sectional study on Japanese workers who visited a clinic for a routine health check-up and asked them to fill out a self-report questionnaire. GERD was defined as episodes of heartburn and/or acid regurgitation at least once a week, and the diagnosis of FD and IBS was based on Rome III criteria. A logistic regression model was used to identify risk factors, and odds ratio (OR) was calculated with 95% confidence intervals (CIs). Results Disease overlaps were found in 160 (6.0%) of the 2680 eligible subjects. Female gender was associated with GERD + IBS (OR=1.99; 95% CI, 1.06-3.75), and FD + IBS (OR=1.72; 95% CI, 1.03-2.85), and lower body mass index was negatively associated with FD + IBS (OR=0.54; 96% CI, 0.34-0.87). Cigarette smoking was a common factor associated with the overlaps: GERD + FD (OR=2.14; 95% CI, 1.22-3.76), GERD + IBS (OR=3.16; 95% CI, 1.75-3.71), FD + IBS (OR=2.26; 95% CI, 1.40-3.66), and GERD + FD + IBS (OR=4.08; 95% CI, 1.66-10.07). The associations between smoking habits and overlaps were stronger in smokers who smoked ≥1 pack per day as compared to those who smoked <1 pack per day. Conclusion Cigarette smoking was significantly associated with overlaps among GERD, FD, and IBS in Japanese adults.